Open Access

Prognostic significance of the expression levels of T‑cell immunoglobulin mucin‑3 and its ligand galectin‑9 for relapse‑free survival in triple‑negative breast cancer

  • Authors:
    • Katsuhiro Yoshikawa
    • Mitsuaki Ishida
    • Hirotsugu Yanai
    • Koji Tsuta
    • Mitsugu Sekimoto
    • Tomoharu Sugie
  • View Affiliations

  • Published online on: May 4, 2022     https://doi.org/10.3892/ol.2022.13318
  • Article Number: 197
  • Copyright: © Yoshikawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

T‑cell immunoglobulin mucin‑3 (TIM‑3) expressed at the T‑cell surface acts as an immune checkpoint when bound by its ligand galectin‑9. Blockade of immunosuppression by the TIM3/galectin‑9 signalling pathway may offer novel therapeutic approaches for cancer immunotherapy. Consistent with this, TIM‑3 expression is associated with poorer prognosis in several different types of cancer, possibly as a result of suppression of anticancer immunosurveillance. A number of studies have now documented some effectiveness of immune checkpoint blockade even in triple‑negative breast cancer (TNBC), which is highly aggressive. However, clinical responses are relatively weak, suggesting that several different pathways may be involved. In this context, the role of the TIM‑3/galectin‑9 checkpoint in TNBC is not clear. The present study aimed to determine the clinicopathological significance of TIM‑3 and galectin‑9 expression in this cancer. To this end, 62 patients with TNBC undergoing surgery at Kansai Medical University Hospital (Hirakata, Japan), but not given neoadjuvant chemotherapy, were examined. Tissue microarrays were employed for immunohistochemistry to analyse associations of TIM‑3 and galectin‑9 expression and their impact on relapse‑free survival relative to other poor prognostic risk factors. Galectin‑9 expression was detected in 49 of 62 patient samples (79%), and TIM‑3 in 30 of them (48.4%). Tumour cell galectin‑9 expression was associated with a more favourable prognosis (P=0.027) as was TIM‑3 expression on tumour‑infiltrating lymphocytes (P=0.007). Multivariate analysis indicated that galectin‑9‑ and TIM‑3‑double‑positivity was significantly associated with a more favourable prognosis compared with galectin‑9 and/or TIM‑3 negativity (P=0.044). Thus, the TIM‑3/galectin‑9 signalling pathway may impact anticancer immune reactions in the tumour microenvironment of patients with TNBC. Further investigation will be necessary to determine the molecular mechanisms underlying these relationships.

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June-2022
Volume 23 Issue 6

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Spandidos Publications style
Yoshikawa K, Ishida M, Yanai H, Tsuta K, Sekimoto M and Sugie T: Prognostic significance of the expression levels of T‑cell immunoglobulin mucin‑3 and its ligand galectin‑9 for relapse‑free survival in triple‑negative breast cancer. Oncol Lett 23: 197, 2022
APA
Yoshikawa, K., Ishida, M., Yanai, H., Tsuta, K., Sekimoto, M., & Sugie, T. (2022). Prognostic significance of the expression levels of T‑cell immunoglobulin mucin‑3 and its ligand galectin‑9 for relapse‑free survival in triple‑negative breast cancer. Oncology Letters, 23, 197. https://doi.org/10.3892/ol.2022.13318
MLA
Yoshikawa, K., Ishida, M., Yanai, H., Tsuta, K., Sekimoto, M., Sugie, T."Prognostic significance of the expression levels of T‑cell immunoglobulin mucin‑3 and its ligand galectin‑9 for relapse‑free survival in triple‑negative breast cancer". Oncology Letters 23.6 (2022): 197.
Chicago
Yoshikawa, K., Ishida, M., Yanai, H., Tsuta, K., Sekimoto, M., Sugie, T."Prognostic significance of the expression levels of T‑cell immunoglobulin mucin‑3 and its ligand galectin‑9 for relapse‑free survival in triple‑negative breast cancer". Oncology Letters 23, no. 6 (2022): 197. https://doi.org/10.3892/ol.2022.13318